How to Get the Most out of our Vaccination Program On The Road to Control Disease Multi-factorial Diseases Management Vaccination Chris Chase Department of Veterinary & Biomedical Sciences South Dakota State niversity Brookings, SD 57007 Credits Immunobiology, 6th edition David Topham, niversity of Rochester Dr. Chris Schneider, niversity of Idaho Dr. Nichols, Australia Bovine Respiratory Disease Complex (BRDC) Single most significant infectious disease in cattle Multifactorial Stress Viruses Bacteria All of these pathogens are in the normal bovine population Incidence in the first 40 days on feed 10 30 days peak challenge p to 90% of morbidity p to 70% of mortality BRDC Major challenge to cattle industry 31% of cattle/calf death in S $625 M impact/year Feedlot Industry 65-79% of sickness 44-72% of death Bovine Respiratory Disease Complex Cost of BRD Mortality Morbidity Hospitalization Medication costs Increasing feeding time Labor costs Subclinical Reduction of ADG and FCR
Disease Triangle Stress Stress is anything that reduces immune response capability Adaptation to intensive production is stressful Anything that improves adaptation will reduce costs and improve production The reason that this condition is seen more in intensive operation rather than extensive Stress Prior to Entry Weaning Saleyards Co-mingling or mixing Transport Dehydration Time off feed Injury Stressors at the Feedlot or in the Cow Herd Co-mingling Injury Water - palability and supply Feed - time to first Pen density Pen total number Handling and movements Pen add-ons Weather extremes Dust COMPETITION Pathogens Viruses Mycoplasma Bacteria ncomplicated respiratory Disease Damage Bacterial pneumonia Stressors Physical Environmental Psychological X Immune System Stress Hormones And Adaptive Response T cell memory Anti-inflammatory Pro-inflammatory Comparison of Changes in Cell-mediated Immunity GC Mechanism Aging Stress Treatment Thymus T-cell proliferation Cytotoxicity IL-2, IFN-γ IL-4, IL-10 TNF-α, IL-1, IL-6 or Direction of arrows indicate increase, decrease or no change compared to corresponding control levels Immunoparalysis Ramirez et al., 1996; Globerson and Effros, 2000; Sapolsky et al., 2000; Biondi, 2001; Galon et al., 2002
Stress will decrease chemotaxis Inflammatory Response What Does Stress Do to Neutrophil Motility and Phagocytosis? Neutrophil Chemotaxis and Phagocytosis What Does MLV BVDV Do to Neutrophil Motility and Phagocytosis? Immune Response-Animal Doesn t Lie Immune response Proinflammatory response necessary Expect Some Side effects No side effects- no response Higher disease Poorer immunity (passive and/or active response) Prevention of BRDC Management Eliminate stress factors where possible Recognize the Critical Period for disease detection (3 weeks that follow weaning; placing on feed; shipping of cattle) Prevention of BRDC Management Avoid co-mingling cattle from different sources during critical 3-week period Keep new cattle close to feed and water Don t over crowd (especially early in feeding period) Control dust and mud Summary Environmental factors Reducing group size is desirable Ventilation and dust control are important Transport time, rest, food water Commingling should be avoided Weaning before shipping decreases stress Gradual feed changes with proper supplements are beneficial
Diet and Immunity oung Calf Immune system doesn t get a free ride- energy consumer- calves on poor nutrition- poor response to vaccines Multiple demands on energy for the calfovervaccination can effect growth and development Calves-Vaccinating prior to acclimation to feed (weaning; feedyard) Acidosis, poor vaccine response Energy Available Maintenance Immune response Growth & Lean Deposition Breeding Heifer Prepartum Animal + Immunization Maintenance Maintenance Energy Available Reproduction Growth & Lean Deposition Energy Available Fetal Development Immunity Growth & Body Condition Postpartum Beef Animal + Immunization Energy Available Maintenance Reproduction Immunity Lactation Nutrition & Immunology Order of importance of nutrients to immune system Energy Protein vitamin A vitamin E Copper, Zinc, Selenium IRON
Summary Energy is important for immune response Vitamin A deficiency can decrease mucosal homing Zinc is very important at times of stress Vitamin E/Selenium important for many immune responses Harvey Dunn (1884-1952) Prairie is My Garden, South Dakota Art Museum Prevention of BRDC Management Vaccines Intranasal Vaccines Nasalgen Day old calves Onset Conducted in young calves (3-8 days of age) Challenged with virulent strains of IBRV, BVD 1, BVD 2, BRSV, PI 3, Pasteurella multocida 21 to 28 days post-vaccination Enforce -3 BRSV Nasal studies 14 day old calves Respiratory Immmunlogy Respiratory Immunology Mucosal Immune Response is the most important defense system Almost all bovine pathogens enter via the airways and the mucosa surface Viruses- BHV-1, BVDV, PI3, BRSV, BRCV Bacteria- M. haemolytica, P. multicida, H. somnus, M. bovis
Mucosal Immunity - Local response Mucosal Immunity - Local response Stop them before they infect When Do We Begin Vaccinating Calves? At a week of age At a month of age At 2-3 months of age Before they are born by vaccinating the cow-high quality colostrum Maximizing Colostrum Production Cow management Nutrition Good balanced diet BCS 6.0-7.0 (on a 9) BCS 3.25-3.75 (on a 5) Cu, Se Zn- Immune Minerals What Respiratory Infectious Agents are Important Calves 3 weeks- 3-4 months Pasteurella multicida Mannheimia (Pasteurella) hemolyticae-herd history Clostridial diseases BRSV- herd history, summer pneumonia Leptosporosis Mycoplasma bovis (pneumonia, inner ear)?? BVDV??? What Respiratory Infectious Agents are Important Calves 3-4 months- 12 months Brucella abortus* Pasteurella multicida Mannheimia (Pasteurella) hemolyticae Leptospirosis Clostridial diseases Mycoplasma bovis-arthritis BVDV BRSV PI3 IBR
Beef Vaccination Schedules Calves (<4 months) Respiratory Diseases MLV Calves on Vaccinated Cows-MLV Intranasal vaccines Depends on Maternal Antibody levels-man MLV IM or SC NOT EFFECTIVE-ONL adjuvanted MLV IM or SC) Inactivated- Well adjuvanted, not affected by Maternal Antibody NOT Vaccinate with MLV BVDV before 1 month Better after 2-3 months of age Beef Vaccination Schedules Calves (>4 months) Respiratory Diseases 2-3 weeks prior weaning MLV-1 dose Inactivated-2 doses At weaning- avoid MLV-Immunosuppressive Inactivated-2 doses 2-3 weeks post weaning MLV-1 dose Inactivated-2 doses Stress + Immunosuppressive Viruses= Super Immunosuppresssion Pregnant Cows and MLV Vaccination IBR and BVDV MLV are immunosuppressive What was the origin of safe in Pregnant Cows Claim? Companies requested safe for use in calves nursing pregnant cows (Beef Claim) SDA decided that it would extend the claim to safe in pregnant cows Animals vaccinated with the same product prior to breeding (within 12 months) Pregnant cow claim is only a safety claim. There is no efficacy data indicating that vaccination during pregnancy had any effect on reproductive health in subsequent pregnancy Twelve month duration of safety Misuse- Opening Pandora s Box Safe in pregnant animals vaccinated with the same product prior to breeding (within 12 months) Safe in pregnant animals NOT without recent vaccination
Beef Cow Vaccination Program Cows-Precalving Inactivated-1 doses Viral-Lepto 4-6 weeks before calving optimal but often given earlier Enteric Disease Vaccines 4-6 weeks before calving Beef Cow Vaccination Program Cows-post calving MLV or Inactivated-Viral (IBR, BVDV)-Lepto-Vibro? 2-4 weeks prior to breeding Beef Cow Vaccination Program Pregnant Cows Vaccinating after the first 40 days of pregnancy will not prevent BVDV PI Precautions MLV-IBR-Corpus Luteum-Necrosis- not in naïve animals- Synchronization protocols- break upgive it at least a month before breeding What about the Effect in Previously Vaccinated Animals? Literature- single paper- MLV no effect on conception Active Interference? Why vaccinate? What about susceptible animals? Summary Pregnant cows have two targets- Pregnant cow claim-safety- not efficacy Pregnant cow is immunosuppressed MLV vaccines can be abortifacient and immunosuppressive Laws of Immunological Common Sense Vaccination of dams 4-6 weeks prior to calving improves colostral antibodies Passive antibodies (colostrum) are protective Vaccinate before shipping Vaccinate at least a few days after shipping- a week or two later is best Interval for boosting needs to be more 21 days- length depends on vaccine Too short a vaccination interval can cause problems
Timing of Boosters Timing and the Adaptive Immune Response- Anamnestic Response 2 response to antigen A Magnitude of specific response 1 response to antigen A 4 8 12 16 20 64 68 72 Days A A What is the Best Time Interval for Boostering? Lymphocyte Lymphocyte proliferation apoptosis to Ag A Timing and Immune Response- oung Animals Primary vs Booster Response Percent Suspectible 100 50 0 0 70% Passive Immunity 21% Window of Susceptibility Active Immunity 7 14 21 28 35 Booster Time Interval and Response 451 Calves Branding time 67 days 3 weeks prior to weaning 167 days Weaning 190 days Group 1 vacc 67d and 190d ~120d interval Group 2 167d and 190d ~25d interval o % seroconverted to each virus was same o No difference in morbidity and mortality, feedlot performance or carcass quality Kirkpatrick et al. 2008 JAVMA 233:136-142 A A Days Post Vaccination A Timing of Boosters MLV 2-3 doses by time 8-10 months Inactivated 2-3 doses by time 8-10 months Combination of MLV and inactivated vaccines Boostering MLV vs Inactivated- se them in combination-better adjuvants Evidence in either sequence MLV/Inactivated or Inactivated/ MLV results in similar responses Grooms et al 2002; Royan 2009
Summary Vaccination of dams 4-6 weeks prior to calving improves colostral antibodies Passive antibodies (colostrum) are protective Vaccinate before shipping Vaccinate at least a few days after shipping- a week or two later is best Summary In general we vaccinate calves too much and too soon No need to vaccinate for BVD before 2-3 months of age (don t do it before 1 month) Better colostrum management, less need to vaccinate Intranasal vaccines in young calf especially for BRSV important- if BRSV is a problem Summary Interval for boosting needs to be more 21 days- length depends on vaccine Too short a vaccination interval can cause problems